The primary goal of Project #2 is to evaluate the long-term outcomes in brain function/structure of two groups of VLBW infants (<1300 g) with anemia of prematurity, who were randomly assigned to either a restrictive or liberal RBC transfusion protocol as part of a previous PPG project. Our aim is to determine whether different RBC transfusion guidelines result in different long-term (at age 13) neurodevelopmental outcomes. Our general hypotheses are: 1) Preterm groups will show structural abnormalities of frontal, prefrontal, hippocampal, cerebellar and white matter brain regions, with the restricted transfusion group showing greater abnormalities. 2) Neuropsychological deficits will be identified in both preterm groups in functions governed by fronto-striatal circuits such as rapid naming, verbal fluency, working memory, fine-motor dexterity, and attention. 3) There will be a relationship between documented brain abnormalities and cognitive deficits. We will accomplish our goal by comparing these two groups at age 13, as well as a matched healthy term control group, on neuropsychological functions and brain structure (MRI). The hypotheses of Project #2 are based on the concept that more restrictive transfusion criteria may decrease the oxygen available to the developing brain and could result in more apnea and hypoxia or create iron depletion, either of which could result in impaired neurodevelopment. The specific neuropsychological functions and brain structures that will be addressed in this study have been selected as those most likely to be impaired by limited brain oxygen delivery or brain iron depletion, either of which could be due to restrictive transfusion criteria or to poorly understood adverse effects of multiple transfusions. This project allows the evaluation of strategies for transfusion management of anemia, which is central to the overall PPG theme. Our specific hypotheses are that more restrictive criteria for transfusion will lead to greater structural abnormalities in specific regions of the brain including frontal-prefrontal cortex, basal ganglia, and hippocampus and cerebellum. These abnormalities will affect functions such as rapid naming, verbal fluency, memory, fine- and gross-motor dexterity, attention and executive functions. More restrictive criteria will also lead to greater behavioral inhibition due to frontalstriatal deficits;but will not lead to differences in more general functions such as language, visual-spatial skills, long-term memory, intelligence, and academic achievement. The study proposed is timely because all of the children will be 13 years old during this study period, allowing examination of long-term effects of the transfusion practices. It is also timely in light of the continuing controversy regarding the most appropriate RBC transfusion guidelines to be used to treat anemia of prematurity. The long-term neuropsychological and brain imaging follow-up of premature anemic infants receiving different transfusion management criteria has never before been examined. This study will provide important findings related to potential adverse effects of transfusion practices on neurodevelopment.